The production of multiplication stimulating activity (MSA) by rat liver cell lines in tissue culture has been shown to be independent of the ability of these cell lines to multiply in serum free media. NSILA-s (non suppressible insulin-like activity) and somatomedin-A compete for MSA tracer binding to receptors in chick embryo fibroblasts, human skin fibroblasts, rat liver cells, and purified rat liver plasma membranes. MSA also binds to a wide variety of cells in culture including cell lines derived from human cancers. The binding pattern for MSA is different than the pattern for epidermal growth factor (EGF) binding. A somatomedin binding protein has been found in rat serum and the size of the binding protein and its serum concentration have been found to be growth hormone dependent. Somatomedin activity has been found to be low in several dwarf mice mutants (Snell, Ames and Little) and normal levels were found in the pygmy mouse.